New perspectives on bioactivity of olive oil – evidence from 1 animal models , human interventions and the use of urinary 2 proteomic biomarkers

29 Olive oil (OO) is the primary source of fat in the Mediterranean diet and has been associated 30 with longevity and a lower incidence of chronic diseases, particularly coronary heart disease. 31 Cardioprotective effects of OO consumption have been widely related with improved lipoprotein 32 profile, endothelial function and inflammation, linked to health claims of oleic acid and phenolic 33 content of OO. With cardiovascular disease being a leading cause of death worldwide, a review 34 of the potential mechanisms underpinning the impact of OO in the prevention of disease is 35 warranted. The current body of evidence relies on mechanistic studies involving animal and cell36 based models, epidemiological studies of OO intake and risk factor, small and large scale human 37 interventions, and the emerging use of novel biomarker techniques associated with disease risk. 38 While model systems are important for mechanistic research nutrition, methodologies and 39 experimental designs with strong translational value are still lacking. This review critically 40 appraises the available evidence to date, with particular focus on emerging novel biomarkers for 41 disease risk assessment. New perspectives on OO research are outlined, especially those with 42 scope to clarify key mechanisms by which OO consumption exerts health benefits. The use of 43 urinary proteomic biomarkers, as highly specific disease biomarkers, is highlited towards a 44 higher translational approach involving olive oil in nutritional recommendations. 45